scholarly journals Mitochondrial calcium handling within the interstitial cells of Cajal

2014 ◽  
Vol 307 (1) ◽  
pp. G107-G121 ◽  
Author(s):  
Shawn A. Means ◽  
Leo K. Cheng
Keyword(s):  
Endoplasmic Reticulum ◽  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Calcium Handling ◽  
Intracellular Ca ◽  
Temporal Model ◽  
Model Geometry ◽  
Spatio Temporal ◽  
Cells Of Cajal ◽  
The Impact

The interstitial cells of Cajal (ICC) drive rhythmic pacemaking contractions in the gastrointestinal system. The ICC generate pacemaking signals by membrane depolarizations associated with the release of intracellular calcium (Ca2+) in the endoplasmic reticulum (ER) through inositol-trisphosphate (IP3) receptors (IP3R) and uptake by mitochondria (MT). This Ca2+ dynamic is hypothesized to generate pacemaking signals by calibrating ER Ca2+ store depletions and membrane depolarization with ER store-operated Ca2+ entry mechanisms. Using a biophysically based spatio-temporal model of integrated Ca2+ transport in the ICC, we determined the feasibility of ER depletion timescale correspondence with experimentally observed pacemaking frequencies while considering the impact of IP3R Ca2+ release and MT uptake on bulk cytosolic Ca2+ levels because persistent elevations of free intracellular Ca2+ are toxic to the cell. MT densities and distributions are varied in the model geometry to observe MT influence on free cytosolic Ca2+ and the resulting frequencies of ER Ca2+ store depletions, as well as the sarco-endoplasmic reticulum Ca2+ ATP-ase (SERCA) and IP3 agonist concentrations. Our simulations show that high MT densities observed in the ICC are more relevant to ER establishing Ca2+ depletion frequencies than protection of the cytosol from elevated free Ca2+, whereas the SERCA pump is more relevant to containing cytosolic Ca2+ elevations. Our results further suggest that the level of IP3 agonist stimulating ER Ca2+ release, subsequent MT uptake, and eventual activation of ER store-operated Ca2+ entry may determine frequencies of rhythmic pacemaking exhibited by the ICC across species and tissue types.

scholarly journals Intracellular Ca2+ release from endoplasmic reticulum regulates slow wave currents and pacemaker activity of interstitial cells of Cajal

2015 ◽  
Vol 308 (8) ◽  
pp. C608-C620 ◽  
Author(s):  
Mei Hong Zhu ◽  
Tae Sik Sung ◽  
Kate O'Driscoll ◽  
Sang Don Koh ◽  
Kenton M. Sanders
Keyword(s):  
Slow Wave ◽  
Interstitial Cells Of Cajal ◽  
Ryanodine Receptors ◽  
Interstitial Cells ◽  
Pacemaker Activity ◽  
Current Clamp ◽  
Anoctamin 1 ◽  
Intracellular Ca ◽  
Inward Currents ◽  
Cells Of Cajal

Interstitial cells of Cajal (ICC) provide pacemaker activity in gastrointestinal muscles that underlies segmental and peristaltic contractions. ICC generate electrical slow waves that are due to large-amplitude inward currents resulting from anoctamin 1 (ANO1) channels, which are Ca2+-activated Cl− channels. We investigated the hypothesis that the Ca2+ responsible for the stochastic activation of ANO1 channels during spontaneous transient inward currents (STICs) and synchronized activation of ANO1 channels during slow wave currents comes from intracellular Ca2+ stores. ICC, obtained from the small intestine of Kit +/copGFP mice, were studied under voltage and current clamp to determine the effects of blocking Ca2+ uptake into stores and release of Ca2+ via inositol 1,4,5-trisphosphate (IP3)-dependent and ryanodine-sensitive channels. Cyclocpiazonic acid, thapsigargin, 2-APB, and xestospongin C inhibited STICs and slow wave currents. Ryanodine and tetracaine also inhibited STICs and slow wave currents. Store-active compounds had no direct effects on ANO1 channels expressed in human embryonic kidney-293 cells. Under current clamp, store-active drugs caused significant depolarization of ICC and reduced spontaneous transient depolarizations (STDs). After block of ryanodine receptors with ryanodine and tetracaine, repolarization did not restore STDs. ANO1 expressed in ICC has limited access to cytoplasmic Ca2+ concentration, suggesting that pacemaker activity depends on Ca2+ dynamics in restricted microdomains. Our data from studies of isolated ICC differ somewhat from studies on intact muscles and suggest that release of Ca2+ from both IP3 and ryanodine receptors is important in generating pacemaker activity in ICC.

A Novel Pacemaker Mechanism Drives Gastrointestinal Rhythmicity

Physiology ◽  
2000 ◽  
Vol 15 (6) ◽  
pp. 291-298 ◽  
Author(s):  
Kenton M. Sanders ◽  
Tamás Ördög ◽  
Sang Don Koh ◽  
Sean M. Ward
Keyword(s):  
Endoplasmic Reticulum ◽  
Gastrointestinal Tract ◽  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Pacemaker Activity ◽  
Cation Conductance ◽  
Inward Currents ◽  
Cells Of Cajal ◽  
Pacemaker Currents

Electric pacemaker activity drives peristaltic and segmental contractions in the gastrointestinal tract. Interstitial cells of Cajal (ICC) are responsible for spontaneous pacemaker activity. ICC remain rhythmic in culture and generate voltage-independent inward currents via a nonselective cation conductance. Ca2+ release from endoplasmic reticulum and uptake by mitochondria initiates pacemaker currents. This novel mechanism provides the basis for electric rhythmicity in gastrointestinal muscles.

The impact of acute stress disorder on gallbladder interstitial cells of Cajal

2020 ◽  
Vol 235 (11) ◽  
pp. 8424-8431
Author(s):  
Zhen‐peng Huang ◽  
Hu Qiu ◽  
Ke Wang ◽  
Wei‐bo Chao ◽  
Hao‐bin Zhu ◽  
...  
Keyword(s):  
Interstitial Cells Of Cajal ◽  
Stress Disorder ◽  
Acute Stress ◽  
Acute Stress Disorder ◽  
Interstitial Cells ◽  
Cells Of Cajal ◽  
The Impact

scholarly journals Gastric Electrical Stimulation Increases The Proliferation of Interstitial Cells of Cajal and Alters Enteric Nervous System in Diabetic Rats

2020 ◽  
Author(s):  
Cai Wang ◽  
Hui Zhang ◽  
Le Zhao ◽  
Tao Gao ◽  
Xia Liu ◽  
...  
Keyword(s):  
Nervous System ◽  
Electrical Stimulation ◽  
Enteric Nervous System ◽  
Interstitial Cells Of Cajal ◽  
Interstitial Cells ◽  
Diabetic Rats ◽  
Gastric Electrical Stimulation ◽  
Enteric Neurons ◽  
Cells Of Cajal ◽  
The Impact

Abstract Background: Lack of interstitial cells of Cajal (ICC) and neuropathy were the most possible pathological mechanisms of diabetic gastroparesis. Gastric electrical stimulation (GES) is a promising way to treat gastroparesis. The aims of the present study were to explore the impact of GES on ICC together with enteric neurons in diabetic rats and the possible mechanisms involved.Methods: Sixty rats were randomized into the normal rats, diabetic rats (DM), diabetic rats with sham GES (DM+SGES), and three diabetic rats with GES (DM+GES1, DM+GES2 and DM+GES3). The proliferation of ICC and expressions of 5-HT2B, nNOS, CHAT, PGP9.5 and GDNF were evaluated by immunofluorescence staining or Western blot. The expressions of 5-HT in blood and tissue were determined by ELISA.Results: (1) The proliferation of ICC was hardly observed in the DM group together with the DM+SGES group but increased in the three DM+GES groups. (2) The expression of 5-HT2B was decreased in the DM group and enhanced in the DM+GES groups. Similarly, the expressions of 5-HT in the blood and distal stomach tissue were increased in the DM+GES groups. (3) Both nNOS labeled neurons and CHAT positive neurons were reduced in myenteric plexus of the DM group, while plenty of these neurons were observed the DM+GES groups. (4) The expression of GDNF protein in the diabetic rats was down-regulated, while GES increased the expression of GDNF.Conclusion: GES improves the proliferation of ICC possibly related with 5-HT/5-HT2B signal pathway, and alters enteric nervous system 52 partly though the GDNF expression.

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